The present invention is directed to the 10 kilodalton polypeptide p10 of a Borna Disease Virus (BDV) and its coding nucleic acid sequence. Both can be used in the detection of, and the vaccination against, a BDV and related infections and diseases.
The Borna Disease virus (BDV) is an enveloped, negative sense, nonsegmented, single-stranded RNA virus which causes Borna Disease (BD), a transmissible polioencephalomyelitis, in susceptible animals. The Borna Disease was originally described in horses and sheep, but cattle, rabbits, goats, deer, llamas, alpacas, cats and ostriches can also be naturally infected. Recent reports indicate that the BDV also can infect humans. The virus can be isolated from the naturally infected hosts. The isolates from different species exhibit high degrees of homology, but it is not clear whether they are the same virus originally described as the causative agent of BD in horses or they are closely related viruses. However, viral proteins from one isolate can react with BDV-specific antibodies in the serum of another species, and vice versa.
There is general agreement that the virus is transmitted through saliva and nasal secretions. Animals become infected by direct contact with secretions or by exposure to contaminated food or water. It is likely that the nose is the main site of viral entry into the body. Contact experiments in horses have shown that persistently infected animals, not presenting overt disease, such as virus carriers, may represent a source of infection. This observation is of eminent importance for the introduction of BDV and BDV-related infection into stables, herds or breeding colonies without a previous history of BD. There is a great need to develop a laboratory based diagnostic test for the detection of BDV and BDV-related infection as well as carriers. There also is a great need to develop a vaccine against these infections.
The BDV is strictly neurotropic and is disseminated by intra-axonal transport from the site of infection, for example through the olfactory nerve, or other cerebral nerve endings terminating in the mucous membrane of the oropharyngeal region. The virus localizes preferentially in certain parts of the brain such as the grey matter, nucleus niger, hippocampus or olfactory bulb, and may spread centrifugally to the peripheral nerves whereby the virus can reach the ganglia of some organs. Involvement of certain regions of the brain may give certain focal symptoms, for example involvement of the nucleus niger may explain the appearance of motor disorder. The clinical expression of BDV and BDV-related infection is variable and is dependent on the virus strain and the species infected. Hence, diagnosis of BDV infection based on clinical signs is often difficult, unless the infected animal or pet presents the classical symptoms of BD. There is a need to develop a laboratory test to detect infection by this virus to aid in the diagnosis of BDV and BDV-related infection and associated diseases.
Traditionally, horses, sheep and cattle are economically important to agriculture. They are also susceptible to BDV and BDV-related infection. More recently, agricultural husbandry has diversified to include llamas and alpacas for their wool, deer for venison, and ostriches for their meat, feathers and skin. Some of these animals are not indigenous and have to be imported. For example, llamas, alpacas and ostriches imported from South America to the United States, and ostriches imported from Africa to Israel. These animals also are susceptible to BDV and BDV-related infection. Importation of virus carriers into domestic herds or breeding colonies may decimate a young and potentially blooming agriculture business. There is a great need in developing a laboratory test to detect the infected animals at the port of entry. More important, recent evidence that BDV and BDV-related infection in cats may cause a neurologic disease and that BDV may infect humans are disturbing, because it raises the concern that BDV-infected cats may be a viral reservoir of human infections. It is necessary to develop a laboratory test to aid the diagnosis of BDV-associated neurological diseases and other BDV diseases in cats and in other mammals, including humans. It also is important to develop an efficacious vaccine against BDV and BDV-related infection in these animals.
Antibodies or immunoglobulins are complex proteins made by lymphocytes of a host in response to foreign substance, proteins or pathogens called antigens. Antibodies can bind antigens. All antibodies have the same overall shape, but each antibody has unique regions that make it fit to one antigen but not to another. As a result of this specificity, an antibody specific for BDV will not bind to wart virus or influenza virus. A specific antibody is made only after the lymphocyte has encountered the antigen. The specific antibody is released into the blood stream, lymph, colostrum, saliva, cerebral spinal fluid and into the lumens of the gastrointestinal, respiratory and urinary tracts. Hence, detection of specific antibodies to BDV, or to any one of the viral proteins, in any one of these body fluid suggests that the host has been exposed to or infected infected with a BDV.